Aerosol-induced immunoglobulin (Ig)-E unresponsiveness to ovalbumin does not require CD8+ or T cell receptor (TCR)-gamma/delta+ T cells or interferon (IFN)-gamma in a murine model of allergen sensitization.
Mice exposed for 20 min daily to aerosolized ovalbumin (OVA) for 10 d at concentrations from 1 to 0.01% OVA made greatly reduced immunoglobulin (Ig)-E responses to subsequent immunogenic OVA challenges, given either intraperitoneally or by aerosol. This IgE-specific unresponsiveness lasted for at least four months. However, these aerosol-treated mice were primed for larger OVA-specific IgG1 and IgG2a responses. The specific reduction in IgE responses was not due to preferential induction of a T helper (Th)-1 response as aerosol OVA- primed mice made greatly reduced Th2 and no detectable Th1 response after rechallenge in vitro. Consistent with this, the increase in circulating eosinophils observed in control Th2-primed mice was absent in aerosol OVA-treated animals. Interferon (IFN)-gamma was not required for this unresponsiveness, as IFN-gamma knockout mice and anti-IFN-gamma antibody-treated wild-type mice had greatly reduced levels of IgE similar to wild-type controls. CD8+ T cells played a relatively small role as IgE responses were reduced to about the same extent in beta2 microglobulin-deficient, or in anti-CD8-treated wild-type mice as in normal mice after aerosol OVA treatment. Similarly, T cell receptor (TCR)-gamma/delta T cells were not required for maximal inhibition of the IgE response. These results demonstrate that exposure to inhaled protein antigens can induce a state of unresponsiveness of CD4+ T cells that results in a prolonged loss of IgE and eosinophil responses to subsequent challenges. This T cell unresponsiveness was shown not to require CD8+ or TCR-gamma/delta+ T cells or IFN-gamma.
Seymour
B W
BW
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Gershwin
L J
LJ
Coffman
R L
RL
D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D001613:beta 2-Microglobulin / Q000502:physiology
D000336:Aerosols; D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta; D001613:beta 2-Microglobulin; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin